The present disclosure, according to specific example embodiments, generally relates to methods of inhibiting the interaction between a S100 molecule and the receptor for advanced glycation end-products (RAGE). In particular, the present disclosure relates to inhibiting the interaction between a S100 molecule and RAGE using cromolyn compounds and/or a C5 compound.
Despite recent advances in understanding the biology of pancreatic cancer and molecular alterations in tumor pathogenesis, pancreatic cancer remains an oncologic challenge, with a 5-year survival rate of less than 5%. Pancreatic adenocarcinoma is arguably the most lethal of all cancers, with more than 95% of patients diagnosed with the disease dying from it, more than half within 6 months. In the United States, it ranks fourth among the leading causes of cancer death, accounting for more than 30,000 deaths annually. There is no effective therapy for pancreatic cancer other than early resection, but only a small percentage of patients are good candidates for surgery. Gemcitabine is the current conventional chemotherapy for pancreatic cancer, and it provides meager benefits. Combinations of gemcitabine with radiation or with other cytotoxic agents have also proven disappointing.
Because of the poor response to these standard forms of therapy, recent efforts have focused on the application of novel, biologically targeted agents aimed at well-known cancer mechanisms. Examples of these approaches include compounds that target vascular endothelial growth factor receptors, e.g., bevacizumab; the epidermal growth factor (EGF) receptor, e.g., cetuximab; the EGFR-activating tyrosine kinase, e.g., erlotinib and gefitinib; and K-ras e.g., farnesyol transferase inhibitor tipifarnib. However, most clinical trials with these agents have shown only a very modest survival advantage when compared to standard gemcitabine treatment.